Navegando por Autor "Götz, Magdalena"
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Artigo Continuous live imaging of adult neural stem cell division and lineage progression in vitro(2011) Costa, Marcos Romualdo; Ortega, Felipe; Brill, Monika S.; Beckervordersandforth, Ruth; Petrone, Ciro; Schroeder, Timm; Götz, Magdalena; Berninger, BenediktLittle is known about the intrinsic specification of adult neural stem cells (NSCs) and to what extent they depend on their local niche. To observe adult NSC division and lineage progression independent of their niche, we isolated cells from the adult mouse subependymal zone (SEZ) and cultured them at low density without growth factors. We demonstrate here that SEZ cells in this culture system are primarily neurogenic and that adult NSCs progress through stereotypic lineage trees consisting of asymmetric stem cell divisions, symmetric transit-amplifying divisions and final symmetric neurogenic divisions. Stem cells, identified by their astro/radial glial identity and their slow-dividing nature, were observed to generate asymmetrically and fast-dividing cells that maintained an astro/radial glia identity. These, in turn, gave rise to symmetrically and fast-dividing cells that lost glial hallmarks, but had not yet acquired neuronal features. The number of amplifying divisions was limited to a maximum of five in this system. Moreover, we found that cell growth correlated with the number of subsequent divisions of SEZ cells, with slow-dividing astro/radial glia exhibiting the most substantial growth prior to division. The fact that in the absence both of exogenously supplied growth factors and of signals provided by the local niche neurogenic lineage progression takes place in such stereotypic fashion, suggests that lineage progression is, to a significant degree, cell intrinsic or pre-programmed at the beginning of the lineage.Artigo Reactive Glia in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog(2013-04-04) Sirko, Swetlana; Behrendt, Gwendolyn; Johansson, Pia Annette; Tripathi, Pratibha; Costa, Marcos Romualdo; Bek, Sarah; Heinrich, Christophe; Tiedt, Steffen; Colak, Dilek; Dichgans, Martin; Fischer, Isabel Rebekka; Plesnila, Nikolaus; Staufenbiel, Matthias; Haass, Christian; Snapyan, Marina; Saghatelyan, Armen; Li-Huei, Tsai; Fischer, André; Grobe, Kay; Dimou, Leda; Götz, MagdalenaAs a result of brain injury, astrocytes become activated and start to proliferate in the vicinity of the injury site. Recently, we had demonstrated that these reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres in vitro. In the present study, we demonstrate that it is only invasive injury, such as stab wounding or cerebral ischemia, and not noninvasive injury conditions, such as chronic amyloidosis or induced neuronal death, that can elicit this increase in plasticity. Furthermore, we find that Sonic hedgehog (SHH) is the signal that acts directly on the astrocytes and is necessary and sufficient to elicit the stem cell response both in vitro and in vivo. These findings provide a molecular basis for how cells with neural stem cell lineage emerge at sites of brain injury and imply that the high levels of SHH known to enter the brain from extraneural sources after invasive injury can trigger this response.Artigo Using an adherent cell culture of the mouse subependymal zone to study the behavior of adult neural stem cells on a single-cell level(2011-11-03) Ortega, Felipe; Costa, Marcos Romualdo; Simon-Ebert, Tatiana; Schroeder, Timm; Götz, MagdalenaA comprehensive understanding of the cell biology of adult neural stem cells (aNSCNSCNSCs) requires direct observation of aNSCNSCNSC division and lineage progression in the absence of niche-dependent signals. Here we describe a culture preparation of the adult mouse subependymal zone (SESEZ), which allows for continuous single-cell tracking of aNSCNSCNSC behavior. The protocol involves the isolation (~3 h) and culture of cells from the adult SESEZ at low density in the absence of mitogenic growth factors in chemically defined medium and subsequent live imaging using time-lapse video microscopy (5–7 d); these steps are followed by postimaging immunocytochemistry to identify progeny (~7 h). This protocol enables the observation of the progression from slow-dividing aNSCNSCNSCs of radial/astroglial identity up to the neuroblast stage, involving asymmetric and symmetric cell divisions of distinct fast-dividing precursors. This culture provides an experimental system for studying instructive or permissive effects of signal molecules on aNSCNSCNSC modes of cell division and lineage progression.